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    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2005-004338-42
    Sponsor's Protocol Code Number:CV185-023
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2006-06-28
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedAustria - BASG
    A.2EudraCT number2005-004338-42
    A.3Full title of the trial
    A Phase 2, Placebo-Controlled, Randomized, Double-Blind, Parallel Arm, Dose Ranging
    Study to Evaluate Safety and Efficacy of Apixaban In Patients with a Recent Acute
    Coronary Syndrome.

    Revised Protocol 01 incorporating Amendment 03

    And Parmacogenetics Blood Sample Amendment 01 dated 17-Feb-2006

    Revised Protocol 02 incorporating Amendment 04 and Admin Letter 01
    A.3.2Name or abbreviated title of the trial where available
    APPRAISE-1
    A.4.1Sponsor's protocol code numberCV185-023
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBristol Myers Squibb International Corporation
    B.1.3.4CountryBelgium
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameApixaban
    D.3.2Product code BMS-562247-01
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApixaban
    D.3.9.1CAS number 503612-47-3
    D.3.9.2Current sponsor codeBMS-562247-01 (laboratory code)
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameApixaban
    D.3.2Product code BMS-562247-01
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApixaban
    D.3.9.1CAS number 503612-47-3
    D.3.9.2Current sponsor codeBMS-562247-01 (laboratory code)
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    ACUTE CORONARY SYNDROMES,NOS
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to evaluate 4 doses of apixaban as compared to placebo over a 26 week treatment period in selected subjects with recent (≤7 days) Acute Coronary Syndrome (ACS) for safety (bleeding) and to determine the optimal dose and regimen of apixaban for use in Phase 3 ACS treatment.
    E.2.2Secondary objectives of the trial
    The secondary safety objectives are:

    • to evaluate the incidence of cardiovascular and all-cause death, non-fatal myocardial infarction, severe recurrent ischemia and non-hemorrhagic stroke during the 30 days after discontinuation of therapy
    • to assess the incidence of adverse events and abnormal clinical laboratory test results.

    The secondary efficacy objectives are:

    • to evaluate the incidence of the composite of cardiovascular death, non-fatal
    myocardial infarction, severe recurrent ischemia and non-hemorrhagic stroke through
    Week 26.
    • to evaluate the incidence of the composite of all-cause death, non-fatal myocardial
    infarction, severe recurrent ischemia and non-hemorrhagic stroke through Week 26.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) Signed written informed consent;
    2) Recent (≤7 days) Acute Coronary Syndrome with:
    a) symptoms of myocardial ischemia (chest pain, dyspnea, etc.) lasting a total of at
    least 10 minutes (see Section 7.2.1)
    And either
    b) elevation in cardiac biomarkers (troponin T or I or creatine kinase-MB) above the
    upper limit of normal
    or
    c) dynamic ST segment deviation [depression or elevation of ≥0.1 mV (1.0 mm)]
    3) Clinically stable, receiving standard care for ACS, including antiplatelet therapy
    [acetylsalicylic acid (ASA) ≤ 165 mg/day, with or without clopidogrel 75 mg/day,
    based on the choice of the treating physician]
    4) Either unknown coronary anatomy or angiographic evidence of atherosclerotic plaque in any major coronary artery significant branch, or coronary bypass graft.
    5) Women who are not of childbearing potential (i.e., who are postmenopausal or
    surgically sterile), and men, ages 18 (or legal age of consent) to 90.

    Plus 1 or more additional risk characteristics from the following:
    1) Age ≥ 65 years
    2) Both elevation in cardiac markers and dynamic ST deviation ≥ 1 mm
    3) Diabetes mellitus
    4) MI within the last 12 months (other than qualifying event)
    5) Cerebrovascular disease [prior (>3 months) ischemic stroke; prior TIA or
    asymptomatic >70% stenosis in either internal carotid artery]
    6) Peripheral vascular disease (claudication with decreased pulses, a prior peripheral
    revascularization procedure, or an ABI <0.9)
    7) Prior symptomatic CHF or a left ventricular ejection fraction <40%
    8) Non-revascularized multivessel CAD (≥2 vessels)
    9) Mild or moderate renal insufficiency (calculated CrCl 30-90 mL/min)
    E.4Principal exclusion criteria
    1) Women of child bearing potential:
    a. Any female who has experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal.
    b. Women who are pregnant or breastfeeding.
    c. Women with a positive pregnancy test on enrollment or prior to study drug
    administration.
    2) Scheduled/planned cardiac catheterization, PCI, CABG or other invasive procedure
    planned in the 26 weeks following randomization;
    3) Persistent severe hypertension, defined as systolic blood pressure of ≥180 mm Hg or diastolic pressure of ≥110 mm Hg
    4) Severe renal dysfunction (calculated creatinine clearance <30 mL/min)
    5) Active bleeding or at high risk for bleeding (e.g., cirrhosis of the liver, any history of
    intracranial hemorrhage, active peptic ulcer disease)
    6) Known coagulopathy
    7) Acute pericarditis or pericardial effusion
    8) Recent stroke (within the last 3 months)
    9) Prior New York Heart Association (NYHA) Class IV;
    *Plus exclusion criteria 23, active hepatobiliary disease
    10) Platelet count ≤100,000/mm3
    11) Hemoglobin < 10 g/dL;
    12) Hematocrit < 30%;
    13) Inability to take aspirin due to allergy or intolerance;
    14) Need for ongoing treatment with a parenteral or oral anticoagulant (see Section
    6.4.1), eg, subjects with mechanical valves, warfarin eligible atrial fibrillation
    15) Need for chronic (>3 months) daily NSAID or chronic high dose ASA use (>325
    mg/day);
    *Plus exclusion criteria 24, strong CYP3A4 inhibitors
    16) Below the legal lower age (country specific);
    17) Participation in another investigational drug or device study within the prior 30 days;
    18) Subjects who participated previously in this or any other study involving
    BMS-562247;
    19) Any condition which, in the opinion of the Investigator, may pose a significant hazard to the subject if he or she is enrolled in the trial;
    20) Subject inability to follow the protocol;
    21) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
    22) Netherlands Specific Exclusion Criteria
    23) Active hepatobiliary disease, based on an ALT or AST > 2X ULN or a Total
    Bilirubin ≥ 1.5X ULN (unless an alternative causative factor [e.g., Gilbert’s
    syndrome] is identified).
    24) Need for ongoing treatment with known strong inhibitors of CYP3A4, for example:
    azole antifungals (itraconazole and ketoconazole), macrolide antibiotics
    (clarithromycin and telithromycin), protease inhibitors (ritonavir, indinavir,
    nelfinavir, atazanavir, and saquinavir), and nefazadone.
    E.5 End points
    E.5.1Primary end point(s)
    Efficacy Analyses
    The primary objective of this study is related to safety. There is no primary efficacy
    outcome. Secondary Efficacy outcomes are:

    • the composite of cardiovascular death, non-fatal myocardial infarction, severe
    recurrent ischemia and non-hemorrhagic stroke occurring through Week 26
    • the composite of all-cause death, non-fatal myocardial infarction, severe recurrent
    ischemia and non-hemorrhagic stroke occurring through Week 26.
    • the composite of all-cause death and myocardial infarction occurring through Week
    26
    • the composite of all-cause death and non-hemorrhagic stroke occurring through Week
    26
    • all-cause death occurring through Week 26
    • cardiovascular death occurring through Week 26
    • the composite of all-cause death and severe recurrent ischemia occurring through
    Week 26.

    Safety Analysis
    The primary safety outcome for this trial is the composite of major bleeding and
    clinically relevant non-major bleeding occurring through the end of treatment.

    The secondary safety outcomes for this trial are 1) all bleeding events, including major bleeding, clinically relevant non-major bleeding and minor bleeding occurring through the end of treatment and 2) the composite of all-cause death, non-fatal myocardial infarction, severe recurrent ischemia and non-hemorrhagic stroke during the 30 days after discontinuation of therapy. Other safety outcome measures will also be assessed, and will include adverse events and abnormal standard clinical laboratory test results, e.g., hemoglobin, platelet count, ALT/AST and creatinine.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Apixaban different doses
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA108
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The last visit for each subject is defined as the Week 26 last treatment visit. The end of the trial is defined as the date of the last follow-up phone call for the last subject, during which adverse events and study endpoints are assessed.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state53
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 1092
    F.4.2.2In the whole clinical trial 1900
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2006-11-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2006-08-14
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2008-05-27
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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